The motility of the gastrointestinal tract is controlled by the automatic nervous system, hormones, and the higher central nerves. It is known that an dysfunction of this control mechanism or an abnormality of the smooth muscle itself causes an anomalous movement of the gastrointestinal tract, thus causing such subjective and objective symptoms as nausea, vomiting, anorexia, dysphagia, abdominal distension, constipation and diarrhea. It is also known that administration of a drug acting on the gastrointestinal smooth muscle is an effective specific treatment of such symptoms and the efficacy of such a drug has been demonstrated clinically as well.
Representative drugs known to act on the smooth muscle include cholinergic drugs such as bethanechol, aclatonium, etc., cholinesterase inhibitors such as neostigmine, etc., dopamine antagonists such as metoclopramide, clebopride, domperidone, etc and drugs acting directly on smooth muscle such as trimebutine, etc., acetylcholine release-promoting drugs such as cisapride and so on.
A furan derivative structurally related to the compound of the invention is ranitidine which is a known antiulcer agent having histamine H.sub.2 -receptor blocking activity. This drug has also been reported to have activity to stimulate motility of the gastrointestinal tract [Scand. J. Gastroenterol., 21 (Suppl. 121), 30 (1986)] but its action is weak. It is also disclosed in U.S. Pat. Nos. 4,128,658, 4,169,855, 4,255,440 and 4,279,819 that ranitidine derivatives of the following formula (A) have antiulcer activity: ##STR1## where T is CH.sub.2, O or S.
Furan derivatives of the following formula (B), which have anti-H.sub.2 histaminic activity, have been disclosed in U.S. Pat. Nos. 4,390,710 and 4,395,553, and EP-A-99122: ##STR2## where T is as defined above.
U.S. Pat. No. 4,031,226 mentions that furancarboxamide derivatives of the following formula (C) have antiemetic activity: ##STR3##
However, with the exception of ranitidine, none of these known compounds are described as ever having gastroprokinetic activity which the compounds of the invention have been demonstrated to have. Further, compounds conforming grossly to the above general formulas (A) and (B) where T is a nitrogen atom are novel compounds.
The above-mentioned cholinergic drugs and cholinesterase inhibitors have been found to cause hypotension and other side effects, while the dopamine antagonists are known to cause extrapyramidal symptoms, hyperprolactinemia and other side effects, and all of them are, thus, limited in utility.
There is a need for a drug which acts directly on the gastrointestinal smooth muscle devoid of adverse effects, a drug to be used safely with therapeutic efficacy in a broad spectrum of diseases associated with gastrointestinal dyskinesia.